The expression of Alkasine Phosphatase (product of the phoA gene) (AP) in E. coli involves the synthesis of inactive protein monomers larger than the mature enzyme and their secretion across the inner membrane, formation of dimers and aggregation with Zn ions followed by processing to a smaller size by an enzyme of the membrane. Mutations to most of these steps have been isolated which affect phoA gene expression. They include two genes of positive control (phoB and phoM) three genes of negative control (phoT, phoS, and pst) one gene which has both positive and negative role (phoR) and one which affects secretion. We plan to define the molecular basis of action of these several genes on the expression of phoA and other phosphate controlled genes in E. coli (the phosphate regulon). Four major tools we are using include: (a) specialized transducing phage either the different control genes or carrying various phosphate controlled genes; (b) genetic fusions in which lacZ has been fused either to the promoters of different control genes or to the promoters of various phosphate controlled genes; (c) transposable drug resistant elements; and (d) plasmids carrying different control genes which have been cloned into suitable cloning vectors.